The project consists of the following studies: 1) Determination of amino acid sequence of normal human G6PD and PGK, and determination of specific amino acid substitutions of variant enzymes. From these studies, molecular pathology of many G6PD and PGK variants associated with hemolytic anemia may be elucidated at the level of our present understanding of hemoglobin variants. Screening and characterization of new G6PD and PGK variants in various populations will be carried out. 2) The problem of selective advantage of the Gd Aplus gene against malaria will be studied by comparison of the infectivity and stability of the normal and Gd Aplus red cells. 3) Amino acid sequence of human embryonic hemoglobin chain (E-chain) will be determined. 4) Amino acid sequence of Beta-chains of various types of thalassemia will be determined. 5) Molecular abnormality of hexosaminidase, pseudocholinesterase, hypoxanthine guanine phosphoribosyl transferase and other enzymes related to genetic disorders will be studied. First, the normal enzymes will be purified to homogeneity and their chemical and biological properties will be studied. With this knowledge and with the use of a specific antibody, the molecular lesion of the variant enzymes from the patient will be studied.